Low Dose Naltrexone (LDN)

Since 2016, Low Dose Naltrexone has been most commonly used to treat such ailments as Multiple Sclerosis, Chronic Fatigue, and Myalgic Encephalopathy, as well as various cancers and autoimmune thyroid diseases. Autoimmune diseases, in particular, seem to respond well to it.

The FDA first approved the drug in 1984. At the time, it was introduced in a 50 mg dose, its purpose being to help heroin and opium addicts. It was ideal for this use since it blocks the effects of such drugs. Naltrexone blocks opioid receptors, while at the same time preventing the reception of beta-endorphins and metenkephalin, the opioid hormones that the adrenal glands and the brain produce. Lots of body tissues have receptors for these enkephalins and endorphins, including essentially each cell of the body’s immune system.

In 1985, Bernard Bihari, MD, working out of a clinical practice in New York City, realized that the effects of a much smaller dose of the drug (approximately 3 mg once each day), was able to enhance a patient’s response to HIV infection.

By the mid-1990s, Dr. Bihari discovered that patients in his practice with cancer (such as pancreatic or lymphoma), could benefit quite a bit in some cases from Low Dose Naltrexone. He also found that people who had an autoimmune disease like lupus showed rapid control of disease activity when put on the drug.

HOW DOES LOW DOSE NALTREXONE WORK?

Over the past twenty years, a great deal of research has been done on Low Dose Naltrexone and its function.

In a November 13, 2003 issue of the New England Journal of Medicine, it was noted that "Opioid-Induced Immune Modulation: ... Preclinical evidence indicates overwhelmingly that opioids alter the development, differentiation, and function of immune cells, and that both innate and adaptive systems are affected.^1,2 Bone marrow progenitor cells, macrophages, natural killer cells, immature thymocytes and T cells, and B cells are all involved. The relatively recent identification of opioid-related receptors on immune cells makes it even more likely that opioids have direct effects on the immune system."

As indicated above. it was first determined that the body’s endorphin secretions (our internal opioids) play an essential role in a beneficial orchestration of the immune system. Recognition of this has now become widespread. Since then, the understanding of LDN’s has been expanded.

Naltrexone’s chemical structure is almost identical to the body’s own endorphin, Met-Enkephalin, also known as Opioid Growth Factor (OGF). Naltrexone exerts its role by blocking the OGF receptor. The OGF receptor is found in a wide range of places including the brain, spinal cord, stomach, small intestines, and the body’s own immune cells. By blocking the OGF receptor, there is a rebound increase in enkephalin and endorphin production, as well as increased opioid receptor sensitivity and opioid receptor production.

In fact, healthy volunteers who have taken LDN have seen their levels of beta-endorphins circling in their blood rise. Animal research conducted by I. Zagon, PhD also noted a clear increase in metenkephalin levels after LDN administration, and that elevated levels usually last for about 18-20 hours.

The net result of the increased levels and activity of endorphins and enkephalins is that they regulate cell growth, including immune cell production. This seems to lead to a shift away from the more cytotoxic T cells. Cytotoxic T cells, when in dysregulation, lead to unfettered inflammation, tissue destruction, and pain.
LDN has been found to protect nerve cells from damage, degeneration, and dysfunction by working on glial cells by blocking toll like receptor (TLR-4).

Glial cells are non-neuronal cells that provide neurons with support and protection. They are present in all of that gray matter in the brain and spinal cord. A special population of glial cells are microglia.
Microglia are scavenger cells that remove infections and damaged neurons. When these cells become overactive, however, they can cause inflammation, cellular deterioration, and even death of neurons.

Microglia express the receptor (TLR-4). The activation of this receptor causes a release of cellular messengers that contributes to excitability of neighboring cells and inflammation. This pathway is the basis of chronic pain and autoimmune disease.

FOR WHAT DISEASES HAS LOW DOSE NALTREXONE BEEN USED?

The disorders listed all share a notable feature: the immune system plays a central role in each of them. Low blood levels of endorphins are usually present, which contributes to the disease-associated immune deficiencies. Such findings suggest that the chance of a beneficial Low Dose Naltrexone effect in a wide variety of autoimmune diseases and common cancers is high.

CANCER

Bladder Cancer
Breast Cancer
Carcinoid
Colon & Rectal
Cancer
Glioblastoma
Liver Cancer
Lung Cancer (Non-Small Cell)
Lymphocytic Leukemia (chronic)
Malignant Melanoma
Multiple Myeloma
Neuroblastoma
Ovarian Cancer
Pancreatic Cancer
Prostate Cancer (untreated)
Renal Cell Carcinoma
Throat Cancer
Uterine Cancer
Lymphoma (Hodgkin's and Non-Hodgkin's)

AUTOIMMUNE

Autoimmune Neurodegenerative
ALS (Lou Gehrig's Disease)
Alzheimer's Disease
Autism Spectrum Disorders
Hereditary Spastic Paraparesis
Multiple Sclerosis (MS)
Parkinson's Disease
Post-Traumatic Stress Disorder (PTSD)
Primary Lateral Sclerosis (PLS)
Progressive Supranuclear Palsy Transverse Myelitis

OTHER DISEASES

Common Cold (URIs)
Emphysema (COPD)
HIV/AIDS
Depression (Major; and Bipolar)

OTHER AUTOIMMUNE DISEASES

Ankylosing Spondylitis
Behcet's Disease
Celiac Disease
Chronic Fatigue Syndrome
CREST syndrome
Crohn's Disease
Dermatomyositis
Dystonia
Endometriosis
Fibromyalgia
Hashimotos Thyroiditis
Irritable Bowel Syndrome (IBS)
Myasthenia Gravis (MG)
Nephrotic Syndrome
Pemphigoid
Primary Biliary Cirrhosis
Psoriasis
Rheumatoid Arthritis
Sarcoidosis
Scleroderma
Sjogrens Syndrome
Stiff Person Syndrome (SPS)
Systemic Lupus (SLE)
Ulcerative Colitis
Wegener's Granulomatosis

THE EFFICACY OF LOW DOSE NALTREXONE HAS BEEN DEMONSTRATED IN THOUSANDS OF CASES

Controlled clinical trials of Low Dose Naltrexone in the treatment of cancer have not yet been accomplished. However, as of March 2004 clinical “off-label” use of the medication by Dr. Bihari in some 450 patients with cancer revealed that more than 60% of them saw some benefit from it. These were patients who had not responded to standard treatments.

Dr. Bihari had follow-ups with 354 of these patients and found that 86 of them had significant shrinkage of tumors, at least a 75% reduction. 125 patients had stabilized or were moving toward remission.

The results attained by Dr. Bihari contrasted with usual cancer treatment outcomes, those being death from cancer or a total cure. It, therefore, is reasonable to surmise that Low Dose Naltrexone treatments represent a viable third alternative, the gradual reduction of tumor mass volume or possible long-term stabilization.

AUTOIMMUNE DISEASES

None of Dr. Bihari’s group of patients who presented with autoimmune diseases have failed to respond to treatment with Low Dose Naltrexone. All of them have experienced a halt in the progression of their conditions. In several of these patients, there has been a marked remission in symptoms and signs of the disease. Many of those in the autoimmune group have multiple sclerosis; there were 400 in Dr. Mihari’s practice. The doctor reported that less than 1% of those 400 experienced a fresh attack of MS while they were kept on nightly therapy with Low Dose Naltrexone.

The treatment of AIDS/HIV has also seen the use of Low Dose Naltrexone since the 1980s, with good effect. There are a score of these patients who even today only use Low Dose Naltrexone and can keep the virus in check. Low Dose Naltrexone, when combined with HAART, is a total preventative for lipodystrophy. It is also a synergistic therapy that bolsters the restoration of CD4 cell levels and diminishes viral breakdowns. As of September 2003, Dr. Bihari treated 350 AIDS patients using Low Dose Naltrexone along with accepted AIDS therapies. Over the seven years before that, he reported that over 85% percent of his patients showed no detectable signs of HIV. This was a much higher success rate than most current AIDS treatments, and there were also no significant side effects. Many HIV/AIDS patients have also been living symptom-free for years at this point by taking only Low Dose Naltrexone with no other medications.

In May of 2016, Nigeria approved a prescribed version of Low Dose Naltrexone for HIV. There was a very successful three-month bridge trial that was performed by NAFDAC, which is Nigeria’s equivalent to the FDA. Approval is currently being granted to Immune Therapies Inc., formerly called TNIB, to market Lodonal (Low Dose Naltrexone) as a non-toxic adjunct therapy for the treatment of HIV/AIDS as well as an immune system regulator. There are also anecdotal reports that indicate that Low Dose Naltrexone can be beneficial for those dealing with primary lateral sclerosis, Alzheimer's Disease, Parkinson's Disease, and ALS, also known as Lou Gehrig’s Disease. Dr. Jaquelyn McCandless has also found that Low Dose Naltrexone in an appropriately reduced dosage when applied as a transdermal cream can be helpful for children with autism.

AT WHAT DOSAGE AND FREQUENCY IS LOW DOSE NALTREXONE TYPICALLY PRESCRIBED?

Treatment doses usually begin in the range of 0.5 to 1.5 mg. Once the dosage has started to be taken on a nightly basis, it is often brought up to 4.5 mg. Low Dose Naltrexone is best taken between 9 pm and 3 am because of the rhythm of the body’s production of master hormones. Most patients take it before going to bed.

For Fibromyalgia, Chronic Fatigue Syndrome, or Hashimoto's Thyroiditis, the starting dose is typically 0.5 mg every week until the daily dose of 4.5 mg is reached, or the dosage where the most relief has been found is reached.
In the case of autoimmune diseases, patients typically begin with 1 mg doses and increase to 4.5 mg over four weeks.
Those with Multiple Sclerosis who are dealing with muscle spasms are advised to start with 3 mg per day and to maintain that dosage.
Those with hyperthyroidism, Hashimoto's Thyroiditis, and those who are taking thyroid hormone replacement medication as well as Low Dose Naltrexone should pay attention to the warnings below.
Those with cancer who are using Low Dose Naltrexone can take similar doses, but these must be avoided the weeks before or after chemotherapy. This does not include daily medications for prostate cancer and tamoxifen.
Pediatric doses are most commonly prescribed at 0.1mg/kg/day

The range of therapeutic dosages for Low Dose Naltrexone is 1.5 to 4.5 mg every night. Dosages as low as 1mg have been found to be effective. Some patients may experience benefits at higher doses up to 12 mg. Patients should give LDN an adequate trial for at least 6 months.

TYPES OF LOW DOSE NALTREXONE

Capsules - It is critical to remember that Low Dose Naltrexone should not be prescribed in SR or slow release form. The capsules should also be filled with a neutral, inactive filler such as lactose or avicel.
Sublingual Drops - Occasionally the drug will need to be purchased as a solution in distilled water. In these cases, 1 mg/ml will be dispensed in a medicine dropper. The solution must be refrigerated.
Cream - Low Dose Naltrexone can also be administered in a 0.5 mg /ml dose as a cream that's applied to the skin. This is most helpful for children or patients who have allergies to colors, excipients, or flavorings found in other forms of Low Dose Naltrexone.

SIDE EFFECTS

Side effects of LDN treatment are reported to be mild. Participants using LDN have even reported it to be slightly more tolerable than placebo (91% vs. 89.5%).⁶

The most commonly reported side effects of low dose naltrexone include insomnia and vivid dreams (37%), diarrhea and headache. Vivid dreams seem to develop as soon as the first dose is taken, and typically decrease over time.⁶

Some patients may benefit from dosing LDN in the morning for several weeks if they experience insomnia and vivid dreams.

CAUTIONARY WARNINGS

Low Dose Naltrexone blocks opioid receptors in the body for 3-4 hours. People who are using medicine that is an opioid agonist, i.e. a narcotic medication like Percocet, a Duragesic patch, Ultram (tramadol) or a codeine-containing medication should not take Low Dose Naltrexone until such drugs are entirely out of their system. Patients who have developed a dependence on daily use of narcotic-containing pain medication will likely require ten days to 2 weeks to be weaned off such drugs entirely before they can safely begin to take Low Dose Naltrexone. During this time they can substitute full doses of non-narcotic pain medications.

2. Patients who take thyroid hormone replacement for Hashimoto's thyroiditis with hypothyroidism should start taking the lowest dosage of Low Dose Naltrexone, 1.5 mg for an adult. Low Dose Naltrexone can lead to a swift decrease in the autoimmune disorder. If this takes place, a rapid reduction in the dose of thyroid hormone replacement will be necessary to avoid the symptoms of hyperthyroidism.

3. Full-dose Naltrexone, or 50 mg, carries a cautionary warning related to the possibility of liver disease. This warning is in place because adverse liver effects have been found in experiments where a dose of 300 mg was administered daily. The 50 mg dosage does not produce this effect, nor do the smaller dosages of 3 mg and 4.5 mg.

4. People who have received transplanted organs and who are taking immunosuppressive medications permanently are cautioned against the use of Low Dose Naltrexone. It can counteract the effects of such drugs.

5. In many, Low Dose Naltrexone is taken along with standard multiple sclerosis medications. All of the conventional MS drugs, though, with the probable exception of Copaxone, are immunosuppressant. Because of this, they are likely to oppose the effects of Low Dose Naltrexone. Many people with MS therefore try to wean themselves off of these other medications if they find that Low Dose Naltrexone is having a positive effect for them.

REFERENCE:

Presented material taken directly from:

http://www.lowdosenaltrexone.org/
http://www.ldnresearchtrust.org/
Roy S, Loh HH. Effects of opioids on the immune system. Neurochem Res 1996;21:1375-1386
Risdahl JM, Khanna KV, Peterson PK, Molitor TW. Opiates and infection. J Neuroimmunol 1998;83:4-18
Makman MH. Morphine receptors in immunocytes and neurons. Adv Neuroimmunol 1994;4:69-82
Younger J, Parkitny L, McLain D. The use of low-dose naltrexone (LDN) as a novel anti-inflammatory treatment for chronic pain. Clin rheumatol 2014; 33(4):451-9.

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To find out more about Low Dose Naltrexone, check out our Blogs:

Discovery of Low Dose Naltrexone

An Introduction to Low Dose Naltrexone

The Interplay between Low Dose Naltrexone and Hashimoto's Thyroiditis

Behavior Medication for Autism Spectrum Disorder (ASD)

Low Dose Naltrexone: The Chronic Pain Management Option 90% Doctors Don’t know About

Multiple Sclerosis: The Signs, Risks, and a Look at Low-Dose Naltrexone Treatment

What all Irritable Bowel Sufferers Need to Know about Low Dose Naltrexone